title: Cocaine-induced vasoconstriction in the human coronary microcirculation: new evidence from myocardial contrast echocardiography.
abstract: BACKGROUND
  Cocaine is a major cause of acute coronary syndrome, especially in young adults; however, the mechanistic underpinning of cocaine-induced acute coronary syndrome remains limited. Previous studies in animals and in patients undergoing cardiac catheterization suggest that cocaine constricts coronary microvessels, yet direct evidence is lacking.
  
  
  RESULTS
  We used myocardial contrast echocardiography to test the hypothesis that cocaine causes vasoconstriction in the human coronary microcirculation. Measurements were performed at baseline and after a low, nonintoxicating dose of intranasal cocaine (2 mg/kg) in 10 healthy cocaine-naïve young men (median age, 32 years). Postdestruction time-intensity myocardial contrast echocardiography kinetic data were fit to the equation y=A(1-e(-βt)) to quantify functional capillary blood volume (A), microvascular flow velocity (β), and myocardial perfusion (A×β). Heart rate, mean arterial pressure, and left ventricular work (2-dimensional echocardiography) were measured before and 45 minutes after cocaine. Cocaine increased mean arterial pressure (by 14±2 mm Hg [mean±SE]), heart rate (by 8±3 bpm), and left ventricular work (by 50±18 mm Hg·mL(-1)·bpm(-1)). Despite the increases in these determinants of myocardial oxygen demand, myocardial perfusion decreased by 30% (103.7±9.8 to 75.9±10.8 arbitrary units [AU]/s; P<0.01) mainly as a result of decreased capillary blood volume (133.9±5.1 to 111.7±7.7 AU; P<0.05) with no significant change in microvascular flow velocity (0.8±0.1 to 0.7±0.1 AU).
  
  
  CONCLUSIONS
  In healthy cocaine-naïve young adults, a low-dose cocaine challenge evokes a sizeable decrease in myocardial perfusion. Moreover, the predominant effect is to decrease myocardial capillary blood volume rather than microvascular flow velocity, suggesting a specific action of cocaine to constrict terminal feed arteries.
authors.affiliation: Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Swaminatha V
authors.initials: SV
authors.lastname: Gurudevan
authors.forename: Michael D
authors.initials: MD
authors.lastname: Nelson
authors.forename: Florian
authors.initials: F
authors.lastname: Rader
authors.forename: Xiu
authors.initials: X
authors.lastname: Tang
authors.forename: Joshua
authors.initials: J
authors.lastname: Lewis
authors.forename: Jimmy
authors.initials: J
authors.lastname: Johannes
authors.forename: J Todd
authors.initials: JT
authors.lastname: Belcik
authors.forename: Robert M
authors.initials: RM
authors.lastname: Elashoff
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Lindner
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Victor
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D001810:Blood Volume / Q000187:drug effects / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology; D003331:Coronary Vessels / Q000000981:diagnostic imaging* / Q000187:drug effects* / Q000502:physiology; D004280:Dobutamine / Q000008:administration & dosage; D004452:Echocardiography / Q000379:methods / Q000592:standards; D006801:Humans; D008297:Male; D055806:Microvessels / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D015203:Reproducibility of Results; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D055815:Young Adult
chemical_list: D002316:Cardiotonic Agents; D014662:Vasoconstrictor Agents; D004280:Dobutamine; D003042:Cocaine
keywords: cocaine; echocardiography; microcirculation; myocardial perfusion imaging